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1.
JAMA Netw Open ; 5(5): e2213606, 2022 May 02.
Article in English | MEDLINE | ID: covidwho-1858512

ABSTRACT

Importance: Data are limited on whether patients with breakthrough COVID-19 infection have the potential to significantly contribute to the spread of SARS-CoV-2. Objective: To compare the secondary attack rate and infectious viral shedding kinetics of SARS-CoV-2 between fully vaccinated individuals (breakthrough infection group) and partially or unvaccinated individuals (nonbreakthrough infection group). Design, Setting, and Participants: This cohort study assessed secondary transmission by analyzing the epidemiologic data of health care workers, inpatients, and caregivers diagnosed with COVID-19 during hospitalization or residence in a tertiary care hospital between March 1, 2020, and November 6, 2021. To evaluate viral shedding kinetics, the genomic RNA of SARS-CoV-2 was measured using polymerase chain reaction and performed virus culture from daily saliva samples of individuals with mild COVID-19 infected with the Delta variant who were isolated in a community facility in Seoul, South Korea, between July 20 and August 20, 2021. Exposures: COVID-19 vaccination. Main Outcomes and Measures: The secondary attack rate and infectious viral shedding kinetics according to COVID-19 vaccination status. Results: A total of 173 individuals (median [IQR] age, 47 [32-59] years; 100 female [58%]) with COVID-19 were included in the secondary transmission study, of whom 50 (29%) had a breakthrough infection. Secondary transmission was significantly less common in the breakthrough infection group than in the nonbreakthrough infection group (3 of 43 [7%] vs 29 of 110 [26%]; P = .008). In the viral shedding kinetics study, 45 patients (median age, 37 years [IQR, 25-49 years]; 14 female [31%]) infected with the Delta variant were included, of whom 6 (13%) were fully vaccinated and 39 (87%) were partially or unvaccinated. Although the initial genomic viral load was comparable between the 2 groups, viable virus in cell culture was detected for a notably longer duration in partially vaccinated (8 days after symptom onset) or unvaccinated (10 days after symptom onset) individuals compared with fully vaccinated individuals (4 days after symptom onset). Conclusions and Relevance: In this cohort study, although the initial genomic viral load was similar between vaccinated and unvaccinated individuals, fully vaccinated individuals had a shorter duration of viable viral shedding and a lower secondary attack rate than partially vaccinated or unvaccinated individuals. Data from this study provide important evidence that despite the possibility of breakthrough infections, COVID-19 vaccinations remain critically useful for controlling the spread of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Cohort Studies , Female , Humans , Kinetics , Middle Aged
2.
Clin Infect Dis ; 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1852999

ABSTRACT

BACKGROUND: Data on the clinical and virological characteristics of the delta variant of SARS-CoV-2 are limited. This prospective cohort study compared the characteristics of the delta variant to other variants. METHODS: Adult patients with mild COVID-19 who agreed to daily saliva sampling at a community isolation facility in South Korea between July and August 2021 were enrolled. Scores of 28 COVID-19-related symptoms were recorded daily. The genomic RNA and subgenomic RNA from saliva samples were measured by real-time reverse-transcriptase-PCR. Cell cultures were performed on saliva samples with positive genomic RNA results. RESULTS: A total of 141 patients (delta group, n = 108 [77%]; non-delta group, n = 33 [23%]) were enrolled. Myalgia was more common in the delta group than in the non-delta group (52% vs. 27%, P = .03). Total symptom scores were significantly higher in the delta group between days 3 to 10 after symptom onset. Initial genomic RNA titers were similar between the two groups; however, during the late course of disease, genomic RNA titers were higher in the delta group. Negative conversion of subgenomic RNA was slower in the delta group (median 9 vs. 5 days; P < .001). The duration of viral shedding in terms of positive viral culture was also longer in the delta group (median 5 vs. 3 days; P = .002). CONCLUSIONS: COVID-19 patients infected with the delta variant exhibited prolonged viable viral shedding with more severe symptoms than those infected with non-delta variants.

3.
J Korean Med Sci ; 37(17): e133, 2022 May 02.
Article in English | MEDLINE | ID: covidwho-1834343

ABSTRACT

BACKGROUND: The potential for a nosocomial outbreak of coronavirus disease 2019 (COVID-19) from a fully vaccinated individual is largely unknown. METHODS: In October 2021, during the time when the delta variant was dominant, a nosocomial outbreak of COVID-19 occurred in two wards in a tertiary care hospital in Seoul, Korea. We performed airflow investigations and whole-genome sequencing (WGS) of the virus. RESULTS: The index patient developed symptoms 1 day after admission, and was diagnosed with COVID-19 on day 4 post-admission. He was fully vaccinated (ChAdOx1 nCoV-19) 2 months before the diagnosis. Three inpatients and a caregiver in the same room, two inpatients in an adjacent room, two inpatients in rooms remote from the index room, and one nurse on the ward tested positive. Also, two resident doctors who stayed in an on-call room located on the same ward tested positive (although they had no close contact), as well as a caregiver who stayed on an adjacent ward, and a healthcare worker who had casual contact with this caregiver. Samples from five individuals were available for WGS, and all showed ≤ 1 single-nucleotide polymorphism difference. CCTV footage showed that the index case walked frequently in the corridors of two wards. An airflow study showed that the air from the corridor flowed into the resident on-call room, driven by an air circulator that was always turned on. CONCLUSION: Transmission of severe acute respiratory syndrome coronavirus 2 from a fully vaccinated index occurred rapidly via the wards and on-call room. Care must be taken to not use equipment that can change the airflow.


Subject(s)
COVID-19 , Cross Infection , COVID-19/epidemiology , Cross Infection/epidemiology , Cross Infection/prevention & control , Disease Outbreaks , Humans , Male , SARS-CoV-2/genetics
4.
Clin Transl Discov ; 2(2): e55, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1819348
6.
Infect Chemother ; 54(1): 102-113, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1780121

ABSTRACT

BACKGROUND: This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC). MATERIALS AND METHODS: A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real time-polymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater. RESULTS: Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration. CONCLUSION: In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).

7.
Infect Chemother ; 54(1): 208-212, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1780117

ABSTRACT

We report a case of coronavirus disease 2019 (COVID-19)-associated radiologically suspected organizing pneumonia with repeated negative Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) results from nasopharyngeal swab and sputum samples, but positive result from bronchoalveolar lavage fluid. Performing SARS-CoV-2 RT-PCR in upper respiratory tract samples only could fail to detect COVID-19-associated pneumonia, and SARS-CoV-2 could be an etiology of radiologically suspected organizing pneumonia.

8.
Korean J Intern Med ; 37(2): 455-459, 2022 03.
Article in English | MEDLINE | ID: covidwho-1737117

ABSTRACT

BACKGROUND/AIMS: Data comparing the antibody responses of different coronavirus disease 2019 (COVID-19) vaccine platforms according to dose with natural severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced antibody responses are limited. METHODS: Blood samples from adult patients with mild and severe COVID-19 and healthcare workers who received ChAdOx1 nCoV-19 vaccine (2nd dose at 12-week intervals) and BNT162b2 vaccine (2nd dose at 3-week intervals) were collected and compared by immunoglobulin G immune responses to SARS-CoV-2 specific spike protein using an in-house-developed enzyme-linked immunosorbent assay. RESULTS: A total of 53 patients, including 12 and 41 with mild and severe COVID-19, respectively, were analyzed. In addition, a total of 73 healthcare workers, including 37 who received ChAdOx1 nCoV-19 and 36 who received BNT162b2, were enrolled. Antibody responses after the first and second doses of the ChAdOx1 nCoV-19 vaccine or the first dose of the BNT162b2 vaccine were similar to those in convalescent patients with mild COVID-19, but lower than those in convalescent patients with severe COVID-19, respectively. However, after the second dose of the BNT162b2 vaccine, the antibody response was comparable to that in convalescent patients with severe COVID-19. CONCLUSION: Our data suggest that the second dose of mRNA vaccination may be more beneficial in terms of long-term immunity and prevention of SARS-CoV-2 variant infection than a single dose of COVID-19 vaccination or homologous second challenge ChAdOx1 nCoV-19.


Subject(s)
Antibody Formation , COVID-19 , SARS-CoV-2 , Adult , Antibody Formation/drug effects , /pharmacology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/pharmacology , COVID-19 Vaccines/therapeutic use , /pharmacology , Humans
9.
Immune Netw ; 21(6): e41, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1704288

ABSTRACT

Correlation between vaccine reactogenicity and immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Thus, we investigated to determine whether the reactogenicity after coronavirus disease 2019 vaccination is associated with antibody (Ab) titers and T cell responses. This study was prospective cohort study done with 131 healthcare workers at tertiary center in Seoul, South Korea. The degrees of the local reactions after the 1st and 2nd doses of ChAdOx1 nCov-19 (ChAdOx1) vaccination were significantly associated with the S1-specific IgG Ab titers (p=0.003 and 0.01, respectively) and neutralizing Ab (p=0.04 and 0.10, respectively) in age- and sex-adjusted multivariate analysis, whereas those after the BNT162b2 vaccination did not show significant associations. T cell responses did not show significant associations with the degree of reactogenicity after the ChAdOx1 vaccination or the BNT162b2 vaccination. Thus, high degree of local reactogenicity after the ChAdOx1 vaccine may be used as an indicator of strong humoral immune responses against SARS-CoV-2.

10.
J Clin Invest ; 131(13)2021 07 01.
Article in English | MEDLINE | ID: covidwho-1556620

ABSTRACT

Seasonal influenza vaccination elicits a diminished adaptive immune response in the elderly, and the mechanisms of immunosenescence are not fully understood. Using Ig-Seq, we found a marked increase with age in the prevalence of cross-reactive (CR) serum antibodies that recognize both the H1N1 (vaccine-H1) and H3N2 (vaccine-H3) components of an egg-produced split influenza vaccine. CR antibodies accounted for 73% ± 18% of the serum vaccine responses in a cohort of elderly donors, 65% ± 15% in late middle-aged donors, and only 13% ± 5% in persons under 35 years of age. The antibody response to non-HA antigens was boosted by vaccination. Recombinant expression of 19 vaccine-H1+H3 CR serum monoclonal antibodies (s-mAbs) revealed that they predominantly bound to non-HA influenza proteins. A sizable fraction of vaccine-H1+H3 CR s-mAbs recognized with high affinity the sulfated glycans, in particular sulfated type 2 N-acetyllactosamine (Galß1-4GalNAcß), which is found on egg-produced proteins and thus unlikely to contribute to protection against influenza infection in humans. Antibodies against sulfated glycans in egg-produced vaccine had been identified in animals but were not previously characterized in humans. Collectively, our results provide a quantitative basis for how repeated exposure to split influenza vaccine correlates with unintended focusing of serum antibody responses to non-HA antigens that may result in suboptimal immunity against influenza.


Subject(s)
Antibodies, Viral/biosynthesis , Influenza Vaccines/immunology , Influenza, Human/immunology , Viral Proteins/immunology , Adult , Age Factors , Aged , Animals , Antibodies, Monoclonal/immunology , Antibodies, Viral/blood , Cohort Studies , Cross Reactions , Eggs/analysis , Humans , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Middle Aged , Polysaccharides/immunology , Vaccination
12.
Viruses ; 13(11)2021 10 22.
Article in English | MEDLINE | ID: covidwho-1481021

ABSTRACT

We conducted a prospective cohort study at a community facility designated for the isolation of individuals with asymptomatic or mild COVID-19 between 10 January and 22 February 2021 to investigate the relationship of viral shedding with symptom changes of COVID-19. In total, 89 COVID-19 adult patients (12 asymptomatic, 16 presymptomatic, 61 symptomatic) were enrolled. Symptom scores, the genomic RNA and subgenomic RNA of SARS-CoV-2 from saliva samples with a cell culture were measured. Asymptomatic COVID-19 patients had a similar viral load to symptomatic patients during the early course of the disease, but exhibited a rapid decrease in viral load with the loss of infectivity. Subgenomic RNA and viable virus by cell culture in asymptomatic patients were detected only until 3 days after diagnosis, and the positivity of the subgenomic RNA and cell culture in symptomatic patients gradually decreased in both from 40% in the early disease course to 13% at 10 days and 4% at 8 days after the symptom onset, respectively. In conclusion, symptomatic patients have a high infectivity with high symptom scores during the early disease course and gradually lose infectivity depending on the symptom. Conversely, asymptomatic patients exhibit a rapid decrease in viral load with the loss of infectivity, despite a similar viral load during the early disease course.


Subject(s)
Asymptomatic Infections , COVID-19/virology , SARS-CoV-2/physiology , Virus Shedding , Adult , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged , Prospective Studies , RNA, Viral/analysis , SARS-CoV-2/isolation & purification , Saliva/virology , Viral Load
13.
N Engl J Med ; 385(17): 1629-1630, 2021 10 21.
Article in English | MEDLINE | ID: covidwho-1442837
14.
Am J Trop Med Hyg ; 105(2): 395-400, 2021 Jun 17.
Article in English | MEDLINE | ID: covidwho-1374604

ABSTRACT

Data on the longevity of humoral and cell-mediated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) are limited. We evaluated the detailed kinetics of antibody and T-cell responses at the acute, convalescent, and post-convalescent phases in COVID-19 patients with a wide range of severity. We enrolled patients with COVID-19 prospectively from four hospitals and one community treatment center between February 2020 and January 2021. symptom severity was classified as mild, moderate, or severe/critical. Patient blood samples were collected at 1 week (acute), 1 month (convalescent), and 2 months after symptom onset (post-convalescent). Human SARS-CoV-2 IgG and IgM antibodies were measured using in-house-developed ELISA. The SARS-CoV-2-specific T-cell responses against overlapping peptides of spike proteins and nucleoprotein were measured by interferon-γ enzyme-linked immunospot assays. Twenty-five COVID-19 patients were analyzed (mild, n = 5; moderate, n = 9; severe/critical, n = 11). IgM and IgG antibody responses peaked at 1 month after symptom onset and decreased at 2 months. IgG response levels were significantly greater in the severe/critical group compared with other groups. Interferon-γ-producing T-cell responses increased between 1 week and 1 month after symptom onset, and had a trend toward decreasing at 2 months, but did not show significant differences according to severity. Our data indicate that SARS-CoV-2-specific antibody responses were greater in those with severe symptoms and waned after reaching a peak around 1 month after symptom onset. However, SARS-CoV-2-specific T-cell responses were not significantly different according to symptom severity, and decreased slowly during the post-convalescent phase.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Severity of Illness Index , T-Lymphocytes/immunology , Acute Disease , Adult , Aged , Antibodies, Neutralizing/blood , COVID-19/blood , COVID-19/pathology , Convalescence , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Interferon-gamma/analysis , Kinetics , Male , Middle Aged , Prospective Studies
15.
J Korean Med Sci ; 36(33): e233, 2021 Aug 23.
Article in English | MEDLINE | ID: covidwho-1370979

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission among non-close contacts is not infrequent. We evaluated the proportion and circumstances of individuals to whom SARS-CoV-2 was transmitted without close contact with the index patient in a nosocomial outbreak in a tertiary care hospital in Korea. From March 2020 to March 2021, there were 36 secondary cases from 14 SARS-CoV-2 infected individuals. Of the 36 secondary cases, 26 (72%) had been classified as close contact and the remaining 10 (28%) were classified as non-close contact. Of the 10 non-close contact, 4 had short conversations with both individuals masked, 4 shared a space without any conversation with both masked, and the remaining 2 entered the space after the index had left. At least one quarter of SARS-CoV-2 transmissions occurred among non-close contacts. The definition of close contact for SARS-CoV-2 exposure based on the mode of droplet transmission should be revised to reflect the airborne nature of SARS-CoV-2 transmission.


Subject(s)
COVID-19/transmission , SARS-CoV-2 , COVID-19/epidemiology , Contact Tracing , Humans , Republic of Korea/epidemiology
17.
Clin Microbiol Infect ; 28(1): 101-106, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1356179

ABSTRACT

OBJECTIVES: The development of a rapid diagnostic test for viable SARS-CoV-2 is important for infection control. Real-time RT-PCR assays detect non-viable virus, and cell culture differentiates viable virus but it takes several weeks and is labour-intensive. Subgenomic RNAs may reflect replication-competent virus. We therefore evaluated the usefulness of subgenomic RNAs for diagnosing viable SARS-CoV-2 in patients with COVID-19. METHODS: Patients with various severities of confirmed COVID-19 were enrolled at a tertiary hospital between February and December 2020. RT-PCR assay results for genomic and subgenomic RNA of SARS-CoV-2 from nasopharyngeal swab, sputum and saliva specimens were compared with cell culture results. RESULTS: A total 189 specimens from 20 COVID-19 patients were tested in genomic and subgenomic PCR assays and cultured on Vero cells. Of these 189 samples, 62 (33%) gave positive culture results, 93 (49%) negative results and the remaining 34 (18%) indeterminate results. Compared with cell culture results, the sensitivities of genomic RNA and subgenomic RNA of the N and S genes were comparable at 100%, but the specificity of subgenomic RNA (N, 65% and S, 68%) was higher than that of genomic RNA (N, 23% and S, 17%, p < 0.001). The mean durations of positive culture and subgenomic RNA were 11.39 ± 10.34 and 13.75 ± 11.22 days after symptom onset (p 0.437), respectively, while that of genomic RNA was 22.85 ± 11.83 days after symptom onset (p < 0.001). DISCUSSION: Our comparison of subgenomic RNA detection with symptom duration and SARS-CoV-2 culture positivity provides a significant advancement on the transmissibility-based approach beyond the detection of SARS-CoV-2 genomic RNA, and warrants further studies on the development of better diagnostic strategy.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19 , RNA, Viral/isolation & purification , SARS-CoV-2 , Animals , COVID-19/diagnosis , Chlorocebus aethiops , Humans , Polymerase Chain Reaction , RNA, Viral/genetics , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Vero Cells
18.
Infect Chemother ; 53(2): 332-341, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1335280

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreaks occur in hospitals in many parts of the world. In hospital settings, the possibility of airborne transmission needs to be investigated thoroughly. MATERIALS AND METHODS: There was a nosocomial outbreak of COVID-19 in a hematologic ward in a tertiary hospital, Seoul, Korea. We found 11 patients and guardians with COVID-19 through vigorous contact tracing and closed-circuit television monitoring. We found one patient who probably had acquired COVID-19 through airborne-transmission. We performed airflow investigation with simulation software, whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: Of the nine individuals with COVID-19 who had been in the hematologic ward, six stayed in one multi-patient room (Room 36), and other three stayed in different rooms (Room 1, 34, 35). Guardian in room 35 was close contact to cases in room 36, and patient in room 34 used the shared bathroom for teeth brushing 40 minutes after index used. Airflow simulation revealed that air was spread from the bathroom to the adjacent room 1 while patient in room 1 did not used the shared bathroom. Airflow was associated with poor ventilation in shared bathroom due to dysfunctioning air-exhaust, grill on the door of shared bathroom and the unintended negative pressure of adjacent room. CONCLUSION: Transmission of SARS-CoV-2 in the hematologic ward occurred rapidly in the multi-patient room and shared bathroom settings. In addition, there was a case of possible airborne transmission due to unexpected airflow.

19.
J Korean Med Sci ; 36(25): e181, 2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1286918

ABSTRACT

Multisystem inflammatory disease in children is a Kawasaki disease like illness occurring after severe acute respiratory syndrome coronavirus 2 infection in children. As the pandemic progresses, similar syndromes were also reported in adult with a decreased incidence. Multisystem inflammatory syndrome in adults (MIS-A) can be characterized with shock, heart failure, and gastrointestinal symptoms with elevated inflammatory markers after coronavirus disease 2019 (COVID-19) infection. Herein, we describe the first case of MIS-A in South Korea. A 38-year-old man presented to our hospital with a 5-day history of abdominal pain and fever. He had been treated with antibiotics for 5 days at the previous hospital, but symptoms had worsened and he had developed orthopnea on the day of presentation. He suffered COVID-19 six weeks ago. Laboratory data revealed elevated white blood cell counts with neutrophil dominance, C-reactive protein, and B-type natriuretic peptide. Chest X-ray showed normal lung parenchyme and echocardiography showed severe biventricular failure with normal chamber size. We diagnosed him as MIS-A and treated with intravenous immunoglobulin and steroid.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/etiology , Abdominal Pain/etiology , Adrenal Cortex Hormones/therapeutic use , Adult , Fever/etiology , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , Republic of Korea , Shock/etiology , Shock/therapy , Systemic Inflammatory Response Syndrome/drug therapy
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